2199-LB: Weight Loss Maintenance following Semaglutide Discontinuation—The Role of Concurrent Lifestyle Intervention

Introduction and Objective: Discontinuation of semaglutide often results in weight regain due to compensatory biological mechanisms, diminishing the long-term benefits. Concurrent use of lifestyle interventions (LI) alongside semaglutide may help mitigate this weight rebound. Methods: We emulated a target trial with an incident new-user design using Veterans Affairs electronic health records. Among individuals without diabetes who initiated semaglutide from 2019 to 2024, 2,403 had concurrent LI enrollment, defined as participating in MOVE! program within 6 months of treatment initiation. These individuals were matched 1:3 to those without LI, using high-dimensional propensity score matching to balance baseline characteristics. Generalized mixed-effects models assessed body weight trajectories from semaglutide initiation through 12 months following discontinuation. Results: Individuals with concurrent LI achieved greater weight loss before semaglutide discontinuation (-8.3% vs. -7.4%, p<0.001). At 12 months following discontinuation, net weight loss remained greater among LI participants (-5.8 ± 0.5%) compared to nonparticipants (-3.3 ± 0.3%, p<0.01) (figure). Conclusion: Concurrent LI was associated with greater weight loss over semaglutide treatment and less regain following discontinuation. These findings underscore the importance of integrating LI with semaglutide therapy to enhance long-term weight management. Disclosure Q.Xue: n/a. M.E.Pavkov: None. L.S.Phillips: Other Relationship; AbbVie Inc, ForaCare, Inc., Diasyst, Inc., Research Support; Janssen Pharmaceuticals, Inc, Boehringer-Ingelheim, Kowa Pharmaceuticals America, Inc, Pfizer Inc. H.Shao: None. P.Li: None. E.Staton: None. M.K.Ali: Advisory Panel; Eli Lilly and Company. R.Chakkalakal: Research Support; National Institute of Diabetes and Digestive and Kidney Diseases, Centers for Disease Control and Prevention. K.Narayan: None. Y.Hong: Consultant; Weight Watchers International. M.K.Shah: None. P.Zhang: None. Funding CDC (U18DP006747)